Pain is a serious, debilitating condition that is undertreated because because of the dose-limiting side effects of currently used therapeutics. Agonists at the cannabinoid (CB) receptors, including delta-9-tetrahydrocannabinol, have been shown to relieve pain in humans, but their use has been limited due to their psychotropic effects and their possible abuse potential. Most studies on the role of CB receptors in analgesia have focused on GB2 receptors in the central nervous system. Recent data have indicated a role for CB2 receptors in the peripheral nervous system in ameliorating both inflammation and the accompanying pain. We propose to develop a new class of analgesics that are CB2 receptor-selective agonists that may exhibit a dual mechanism of action to provide a one/two punch in alleviating inflammatory pain by acting on peripheral neurons to inhibit pain transmission and by reducing inflammation. Adolor Corporation is a biopharmaceutical company with a proven ability to discover and develop non-narcotic analgesic that lack central nervous system liabilities. We will use our expertise to discover and develop CB2 receptor-selective agonists that are effective analgesics in inflammatory pain. PROPOSED COMMERCIAL APPLICATION: Not Available